Arrestin-like, N-terminal (IPR011021)

Overlapping homologous superfamilies

Domain relationships

None.

Description

G protein-coupled receptors are a large family of signalling molecules that respond to a wide variety of extracellular stimuli. The receptors relay the information encoded by the ligand through the activation of heterotrimeric G proteins and intracellular effector molecules. To ensure the appropriate regulation of the signalling cascade, it is vital to properly inactivate the receptor. This inactivation is achieved, in part, by the binding of a soluble protein, arrestin, which uncouples the receptor from the downstream G protein after the receptors are phosphorylated by G protein-coupled receptor kinases. In addition to the inactivation of G protein-coupled receptors, arrestins have also been implicated in the endocytosis of receptors and cross talk with other signalling pathways. Arrestin (retinal S-antigen) is a major protein of the retinal rod outer segments. It interacts with photo-activated phosphorylated rhodopsin, inhibiting or 'arresting' its ability to interact with transducin [PMID: 15335861]. The protein binds calcium, and shows similarity in its C terminus to alpha-transducin and other purine nucleotide-binding proteins. In mammals, arrestin is associated with autoimmune uveitis.

Arrestins comprise a family of closely-related proteins that includes beta-arrestin-1 and -2, which regulate the function of beta-adrenergic receptors by binding to their phosphorylated forms, impairing their capacity to activate G(S) proteins; Cone photoreceptors C-arrestin (arrestin-X) [PMID: 7720881], which could bind to phosphorylated red/green opsins; and Drosophila phosrestins I and II, which undergo light-induced phosphorylation, and probably play a role in photoreceptor transduction [PMID: 8452755, PMID: 1517224, PMID: 2158671].

The crystal structure of bovine retinal arrestin comprises two domains of antiparallel beta-sheets connected through a hinge region and one short alpha-helix on the back of the amino-terminal fold [PMID: 9495348]. The binding region for phosphorylated light-activated rhodopsin is located at the N-terminal domain, as indicated by the docking of the photoreceptor to the three-dimensional structure of arrestin.

The N-terminal domain consists of an immunoglobulin-like beta-sandwich structure and is found in arrestin and related proteins. For example, thioredoxin-interacting protein (TXNIP) matches the arrestin N domain [PMID: 18664266, PMID: 23519408].